- Email: [email protected]
Milk Lipids | Nutritional Significance
Nutritional Significance N M O’Brien and T P O’Connor, University College, Cork, Ireland ª 2011 Elsevier Ltd. All rights reserved.
Introduction Lipid is the collective term for a diverse range of molecules which have in common the characteristic that they are insoluble in water but soluble in organic solvents, such as ether or chloroform. This range of molecules includes triglycerides (also known as triacylglycerols), other glycerides, phospholipids, sterols, fatty acids, fat-soluble vitamins, all of which have nutritional significance. The overwhelming majority of lipid molecules in milk (approximately 98%) are triglycerides, with small amounts of sterols and phospholipids as the next most important categories. Lipids typically contribute approximately 40% of total energy in Western diets. This level has fallen slightly in recent decades in many countries due to the availability and promotion of low-fat and reduced-fat foods. Milk and milk products typically contribute about 20% of daily fat intake in Western countries, that is, approximately 8–10% of total energy intake. Lipids are significant in the diet in a wide variety of ways. They contribute to the palatability of foods by influencing taste, texture, and mouthfeel. They provide a concentrated source of food energy (9 kcal g1 or 38 kJ g1). Lipids, when deposited as body fat, help protect vital body organs and provide a store of energy for long-term exertion. Food lipids are a source of fat-soluble vitamins (A, D, E, K) and essential fatty acids (linoleic acid and -linolenic acid). Considerable research effort over many decades has focused on the health effects of food (including milk) lipids. Dietary lipid intakes have been related to the so-called ‘diseases of affluence’, such as coronary heart disease (CHD), stroke, and certain cancers. However, in discussing the putative role of dietary lipids, it is important to note the multifactorial etiology of these diseases, that is, there are other risk factors, such as cigarette smoking, hypertension, genetic factors, obesity, diabetes, and exercise level. Indeed, many other dietary factors apart from lipid intake are known to influence chronic disease risk, for example, the protective effects of high intakes of fruit and vegetables are well recognized. Thus, when discussing the health effects of milk lipids in isolation, it is important to emphasize that no food or food constituent, such as fat, should be considered healthy or unhealthy per se. All foods and food constituents are to be considered in the context of overall dietary intake, that is,
one can discuss healthy/unhealthy diets but not individual foods or food constituents.
Metabolism of Lipids Digestion Lipids are a heterogeneous group of molecules which are soluble in nonpolar solvents. Digestion of lipids must take place in the intestinal tract which is an aqueous polar environment and subsequent lipid transport in the blood is also in an aqueous environment. However, as described below, the body has devised means for overcoming this problem. Digestion of fat is initiated by the action of lingual lipase which is secreted in the mouth. However, the major site of fat digestion is the duodenum. The churning action of the stomach creates a crude oil-in-water emulsion of the fat prior to its entry into the duodenum. In the duodenum, the emulsification of fat is enhanced by the action of bile salts and phospholipids which are released from the gall bladder. Pancreatic juice supplies lipase which catalyzes the hydrolysis of triglycerides to fatty acids. Fatty acids are cleaved from positions 1 and 3 of the triglycerides, resulting in 2-monoglycerides. Pancreatic lipase has a poor ability to cleave the fatty acid from position 2. However, a process known as acyl migration may occur and the fatty acid may move to position 1 and subsequently be cleaved by lipase. Additionally, the 2-monoglycerides can be absorbed directly without further hydrolysis. Bile acids play a key role in facilitating the action of pancreatic lipase on triglycerides. The bile acid molecules have both hydrophobic and hydrophilic regions. The former region interacts with the oil surface of the fat droplets while the latter region interacts with the aqueous phase in the duodenum. The association of the bile acids with the oil droplets also results in a negative charge on the surface of the droplets. This negative charge causes pancreatic co-lipase to be attracted to the surface of the oil droplets. Thus, a complex of bile acids, pancreatic lipase, and co-lipase act at the oil–water interface to release fatty acids from the triglyceride molecules. A pancreatic cholesteryl hydrolase releases free fatty acids from any cholesteryl esters present in the duodenum. Phospholipase A cleaves fatty acids from phospholipids to form lysophospholipids.
711
712 Milk Lipids | Nutritional Significance
It has been shown that short-chain fatty acids, for example, butyric acid which is commonly found in position 3 of milk fat triglycerides, are released more rapidly from triglycerides by lipase action than longer-chain fatty acids. However, due to the relatively long time that fat resides in the duodenum, breakdown of triglycerides to fatty acids is virtually complete. However, malabsorption of fat and the appearance of significant amounts of fat in the feces (steatorrhea) may occur in diseased states if insufficient pancreatic lipase, colipase, and bile salts are secreted into the duodenum or if the intestinal mucosal cells become diseased due to severe bacterial infection or conditions such as coeliac disease.
Absorption and Transport of Fats in the Body Fatty acids with fewer than 12 carbons are generally absorbed directly across the intestinal wall into the bloodstream where they are bound to plasma albumin and transported to the liver. Long-chain fatty acids, monoglycerides, cholesterol, and lysophospholipids form micelles in the gut with bile acids. These are then absorbed by the enterocytes that line the gut. In the enterocytes, the lipid digestion products are reassembled into triglycerides, cholesterol esters, and phospholipids. These molecules are immiscible or poorly miscible with water. This is a major issue as these molecules must be transported by the blood (an aqueous environment) throughout the body. This problem is overcome by the association of absorbed lipid molecules with proteins to form lipoproteins. The proteins perform a dual role. Because of their amphiphilic nature, the proteins facilitate transport of lipids in the bloodstream. Second, the proteins (mainly a protein called apolipoprotein B-48, which is present in chylomicrons) allow the lipoprotein particles to be recognized by receptors on cell surfaces throughout the body, thus facilitating the controlled uptake of lipoprotein particles from the bloodstream. Chylomicrons are the lipoprotein particles that are assembled in the enterocytes following digestion and absorption of dietary fat from the gut. The chylomicrons enter the lymphatic system and subsequently the blood following their release from the enterocytes. The blood enzyme, lipoprotein lipase, is involved in releasing free fatty acids from triglycerides in the chylomicrons. These fatty acids are taken up by tissues (e.g., for storage as triglycerides in adipose tissue or metabolism in muscle tissue) and the remainder of the chylomicron particles (remnants) may pass to the liver. Triglycerides and cholesterol may also be synthesized directly in the liver rather than derived from the diet. The triglycerides synthesized in this manner are transported
mainly in the bloodstream in lipoprotein particles called very low density lipoproteins (VLDL). Cholesterol is transported primarily in either low-density lipoproteins (LDL) or high-density lipoproteins (HDL). Thus, all lipoproteins contain proteins, triglycerides, phospholipids, cholesteryl esters, and cholesterol in varying amounts which account for the differences in their density.
Lipids and Obesity A considerable body of evidence worldwide indicates that obesity is associated with increased risk of morbidity and mortality from chronic diseases such as CHD and certain cancers. Dietary guidelines worldwide advise individuals to maintain desirable body weight by controlling food intake and by undergoing regular aerobic exercise. It is also recognized that fat distribution in the body is important in predicting risk for chronic diseases. Central obesity, involving fat deposition around the waist and upper body, is a significant risk factor for CHD. Lower body obesity, involving fat deposition around the hips and thighs, is a much lower risk factor. As noted earlier, the energy value (known as the Atwater factor) for triglycerides is about 9 kcal g1 (38 kJ g1). This compares with approximately 4 kcal g1 (17 kJ g1) for both carbohydrates and proteins. Thus, the more fat in the diet, the more energy-dense it is. This energy density, however, makes fat a more attractive energy store in the body. The degree of digestibility of a fat influences the metabolizable energy available to the body. Most fats, including milk fat, are digested almost completely by healthy individuals. However, long-chain (over 18 carbons) saturated fatty acids are slightly less well digested and absorbed than shorter-chain fatty acids. On the other hand, medium- and short-chain fatty acids have lower metabolizable energy values as they undergo different pathways of metabolism from longer-chain fatty acids. These short- and medium-chain fatty acids are absorbed primarily into the portal blood and metabolized in the liver rather than stored in adipose tissue. Milk fat from ruminant animals contains significant amounts of short-chain fatty acids; about one-third of milk fat triglycerides contain a butyric acid residue. A number of studies have addressed the issue of whether dairy consumption is inversely associated with reduced risk of the metabolic syndrome (obesity, high blood pressure, abnormal blood lipids). Pereira and colleagues reported a 70% decrease in risk of the metabolic syndrome over a 10-year period in individuals with higher levels of dairy product intakes.
Milk Lipids | Nutritional Significance
Lipids and Coronary Heart Disease CHD is the major cause of mortality in Western societies. CHD involves the inability of the coronary arteries to supply sufficient blood, and hence oxygen, to the heart muscle, a portion of which may then die. A heart attack (infarction) is a sudden event involving blockage (thrombosis) of a coronary artery by a blood clot. If significant atherosclerosis is present, that is, an accumulation of plaque deposit in the artery lining resulting in a narrowing of the arteries, the formation of a blood clot is likely to be more serious and often fatal. The ‘lipid hypothesis’, that is, that the etiology of CHD is influenced by dietary fat intake, has been researched extensively for many decades. This hypothesis is that dietary fat, in particular saturated fat, results in an elevation of the blood cholesterol level, which over time results in atherosclerosis. Eventually, a coronary artery thrombosis may occur, resulting in a heart attack. It is thought that atherosclerosis is initiated by damage to a blood vessel wall. This damage may result from factors such as the action of lipid free radicals, reactive oxygen species, infective agents, mechanical stress due to hypertension, and autoimmune reactions. Smooth muscle cells and immune system cells known as macrophages have been shown to accumulate at the site of blood vessel damage. Lipids, principally cholesteryl esters, begin to accumulate at the point of damage as a form of plaque. This atherosclerotic plaque tends to accumulate macrophages which become engorged with lipids, principally from low density lipoprotein (LDL). These lipidengorged macrophages are known as ‘foam cells’. The ability of dietary fat intake to modulate blood lipid levels has been recognized for nearly a century. Landmark studies were conducted in the 1960s by two independent research groups led by Ancel Keys and Mark Hegsted which systematically evaluated the effects of different types of dietary lipids on blood lipid levels in human subjects maintained under strictly controlled metabolic ward conditions. The human subjects were fed a wide range of fats and oils of varying fatty acid composition. These studies led to the development of equations that predicted the changes that would occur in blood cholesterol level following changes in the intake of dietary saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), and cholesterol. Keys and Hegsted independently showed that SFAs were approximately twice as effective in raising blood cholesterol level as PUFAs. Dietary cholesterol intake had a relatively minor influence on blood cholesterol level. These early investigators studied the effects of dietary fat on total blood cholesterol and did not discriminate between different lipoprotein fractions. It is now recognized that dietary parameters influence the
713
levels of different lipoprotein fractions in different ways. Furthermore, it has been demonstrated clearly that the levels of different lipoprotein fractions are related to the risk of CHD in different ways. Elevated levels of LDL have been shown to be a major risk factor for CHD. Likewise, low levels of HDL are a risk factor for CHD. Research findings indicate that dietary intake of different SFAs influences blood cholesterol level to different degrees. Short- and medium-chain fatty acids (4:0 to 10:0), which are found in ruminant milk fat, have little or no effect on blood cholesterol level; furthermore, stearic acid (18:0) has little effect on blood cholesterol. Thus, only lauric (12:0), myristic (14:0), and palmitic (16:0) acids have a significant effect on blood cholesterol and, in particular, LDL cholesterol level. Monounsaturated fatty acids (MUFAs), in particular oleic acid (18:1), have been evaluated for their ability to influence blood cholesterol level. Data indicate that MUFAs, when substituted for SFAs, tend to reduce total blood cholesterol level and, in particular, again, LDL cholesterol. PUFAs of the n–6 family (linoleic, 18:2, being the most important in the diet) have been shown to reduce blood cholesterol level. On the other hand, PUFAs of the n–3 family (primarily -linolenic, 18:3, from plant oils and eicosapentaenoic, 20:5, and docosahexaenoic, 22:6, from fish oils) tend to lower blood triglyceride level to a greater extent than the cholesterol level. Many of the studies on the effects of fatty acids on blood cholesterol have been highly controlled experiments. Prudence is required in extrapolating the results of these studies to free-living populations where people eat a wide variety of fats as part of a mixed diet. Milk fat is hypercholesterolemic when evaluated in controlled experiments. However, epidemiological studies on freeliving populations tend to indicate that intake of milk and milk products does not increase blood cholesterol level significantly. Indeed, studies of the Masai tribe in east Africa indicate that they have very low blood cholesterol levels on a traditional diet rich in milk (primarily fermented) and other animal products. It has been suggested that the Masai may have low blood cholesterol levels due to their low caloric intake and, perhaps, an inherited ability to regulate blood cholesterol level at a low value. Other researchers have suggested that milk contains an unknown cholesterol-lowering factor which counteracts the theoretical hypercholesterolemic effect of milk SFA. However, evidence for such a factor is scant. Further work has investigated the possibility that cultured and culture-containing milk products may be hypocholesterolemic. There is some evidence that increased gut colonization by lactobacilli, whether by ingestion of culture-containing products or by
714 Milk Lipids | Nutritional Significance
manipulation of gut pH to favor lactobacilli, may modify cholesterol metabolism. However, the evidence, at best, suggests that lactobacilli are responsible for only small reductions in blood cholesterol.
Conjugated Linolenic Acid (CLA) in Milk Fat Extensive hydrogenation of ingested PUFAs occurs in the rumen of ruminants, catalyzed by the diverse microflora present. A further effect observed in the rumen is the possible disruption of the original methylene-interrupted (unconjugated) sequence of cis double bonds. Cis–trans isomerization may occur and double bonds may migrate along the fatty acid chain. A cis–trans conjugated double bond sequence may evolve: CH3 ðCH2 Þ4 CH ¼ CH CH2 CH ¼ CH ðCH2 Þ7 cis
cis
COOHð9-cis;12-cis-18:2; linolenic acidÞ
is converted to CH3 ðCH2 Þ5 CH ¼ CH CH ¼ CH ðCH2 Þ7 COOH trans
cis
ð9-cis;11-trans 18:2; conjugated linolenic acid; CLAÞ
9-cis,11-trans-CLA is the principal isomer found (about 90% of total CLA) in biological systems but other isomers of CLA have also been identified. Milk fat and dairy products have very high concentrations of CLA, which vary with season and stage of lactation. Cheese is the best dietary source of CLA, with reported levels of 0.6 mg g1 fat in blue cheese, 1.9 mg g1 fat in Parmesan, and up to 8.8 mg g1 fat in processed cheeses containing whey protein concentrate. CLA is also found in meat from ruminant animals. Over the last two decades, there has been significant research effort on the potential health effects of CLA ingestion. Data indicate that CLA is anticarcinogenic in animal models. It has been suggested that it may be partly responsible for the reduced risk of breast cancer that has been reported in women with high milk consumption. The mechanism by which CLA may exert an anticarcinogenic effect is unclear. It may act as an antioxidant, it may influence eicosanoid metabolism, and it may inhibit biosynthesis of proteins and/or polynucleotides that may be involved in the cancer process. It has been clearly shown that dietary CLA is incorporated into body tissues, such as adipose tissue, human milk, and blood cells. For example, one study has shown that the consumption of 112 g Cheddar cheese per day for 4 weeks significantly increased the level of CLA in blood.
Lipids in Infant Nutrition There is universal agreement that human milk is the most appropriate food for healthy human babies born at full term. However, as many mothers do not wish or are unable to breast feed, a need has arisen for infant formulae, most of which are based on cow’s milk. The formulae try to mimic the composition of human milk to the greatest degree possible, although it is impossible to fully achieve this objective. The concentrations of proteins and salts (sodium) in cow’s milk are too high for infants. The fatty acid composition of cow’s milk fat also differs very significantly from human milk fat. Furthermore, human milk fat tends to contain slightly more cholesterol than cow’s milk fat. The level of short-chain fatty acids (4:0, 6:0, 8:0, and 10:0) is much higher and the level of long-chain saturated acids (14:0, 16:0, and 18:0) is significantly higher in cow’s milk than in human milk fat. Conversely, the content of MUFAs (primarily 18:1 but also 16:1) is significantly higher in human milk fat. Furthermore, the level of PUFAs in human milk fat is considerably higher than in ruminant milk fat; the long-chain n–3 PUFAs, which are present at trace levels in cow’s milk fat, are present at quite high levels in human milk fat. Newborn human babies have a significant need for lipids for membrane synthesis, particularly in the brain and nervous system. High levels of arachidonic (20:4, n–6) and docosahexaenoic (22:6, n–3) are present in membrane lipids of the brain and nervous system. The levels of their respective precursors, linoleic (18:2, n–6) and -linolenic (18:3, n–3), are much lower. The optimum ratios of n–3 to n–6 fatty acids and of precursors (18:2 and 18:3) to products (20:4 and 22:6) in infant formulae have not yet been definitively elucidated. However, it has been suggested that long-chain n–3 fatty acids and long-chain n–6 fatty acids should provide 0.25–0.5% and 0.35–0.7% of energy, respectively. Furthermore, the need for n–6 linoleic and n–3 -linolenic acids has been estimated to be 5–6 and 1% of energy, respectively. In the past, higher levels of linoleic acid have been used but there is now increasing recognition of the importance of n–3 fatty acids.
Conclusions Milk lipids play a positive role in the diet as a source of energy, fat-soluble vitamins, and essential fatty acids. Milk lipids also contribute to the palatability of the diet. Concerns have been expressed regarding the hypercholesterolemic effect of dietary SFAs. Milk lipids from ruminant animals are rich in short-chain fatty acids which do not exert a hypercholesterolemic effect. Of the
Milk Lipids | Nutritional Significance
longer-chain fatty acids in milk fat, only 12:0, 14:0, and 16:0 exert a significant hypercholesterolemic effect in controlled feeding trials with human subjects. However, the evidence that milk intake in free-living populations is hypercholesterolemic is poor. There is some evidence that CLA present in milk fat may exert beneficial health effects. While a reduction in lipid intake, including milk lipids, may be beneficial for obese and overweight individuals, it is important to place a reduction of dietary fat intake for the general population in the context of the need to alter other practices such as smoking and exercise, and control of blood pressure. An optimum diet should emphasize moderation and variety. Milk and milk lipids can certainly play their part in such a diet. See also: Butter and Other Milk Fat Products: Fat Replacers. Dehydrated Dairy Products: Infant Formulae. Milk Lipids: Conjugated Linoleic Acid. Cholesterol: Factors Determining Levels in Blood; Removal of Cholesterol from Dairy Products. Nutrition and Health: Nutritional and Health-Promoting Properties of Dairy Products: Contribution of Dairy Foods to Nutrient Intake. Vitamins: Vitamin A; Vitamin E; Vitamin K; Vitamin B12; Folates; Biotin (Vitamin B7); Niacin; Pantothenic Acid; Vitamin B6; Thiamine.
Further Reading Astrup A (2006) How to maintain a healthy body weight. International Journal of Vitamin and Nutrition Research 76: 208–215. Biong AS, Miller H, Seljeflot I, Veierod MB, and Pedersen JI (2004) A comparison of the effects of cheese and butter on serum lipids,
715
haemostatic variables and homocysteine. British Journal of Nutrition 92: 791–797. Elwood PC, Pickering JE, Fehily AM, Hughes J, and Ness AR (2004) Milk drinking, ischaemic heart disease and ischaemic stroke. II. Evidence from cohort studies. European Journal of Clinical Nutrition 58: 718–724. German JB, Gibson RA, Krauss RM, et al. (2009) A reappraisal of the impact of dairy foods and milk fat on cardiovascular disease risk. European Journal of Nutrition 48: 191–203. Gurr MI (1999) Lipids in Nutrition and Health: A Reappraisal pp. 221. Bridgewater, UK: The Oily Press. Hegsted DM, McGandy RB, Myers ML, and Stare FJ (1965) Quantitative effects of dietary fat on serum cholesterol in man. American Journal of Clinical Nutrition 17: 281–295. Keys A, Anderson JT, and Grande F (1965) Serum cholesterol response to changes in the diet. IV. Particular saturated fatty acids in the diet. Metabolism 14: 776–787. Motard-Belanger A, Charest A, Grenier G, Paquin P, Chouinard Y, and Lemeieux S (2008) Study of the effect of trans fatty acids from ruminants on blood lipids and other risk factors for cardiovascular disease. American Journal of Clinical Nutrition 87: 593–599. Ness AR, Davey Smith G, and Hart C (2001) Milk, coronary heart disease and mortality. Journal of Epidemiology and Community Health 55: 379–382. Oh K, Hu FB, Manson JE, Stampfer MJ, and Willett WC (2005) Dietary fat intake and risk of coronary heart disease in women: 20 years of follow-up of the nurses’ health study. American Journal of Epidemiology 161: 672–679. Parodi PW (2009) Has the association between saturated fatty acids, serum cholesterol and coronary heart disease been over emphasized? International Dairy Journal 19: 345–361. Pereira MA, Jacobs DR, Jr., Van Horn L, Slattery ML, Kartashov AI, and Ludwig DS (2002) Dairy consumption, obesity, and the insulin resistance syndrome in young adults. Journal of the American Medical Association 287: 2081–2089. Tholstrup T (2006) Dairy products and cardiovascular disease. Current Opinion in Lipidology 17: 1–10. Tricon S, Burdge GC, Jones EL, et al. (2006) Effects of dairy products naturally enriched with cis-9, trans-11 conjugated linoleic acid on the blood lipid profile in healthy middle-aged men. American Journal of Clinical Nutrition 83: 744–753. Zemel MB (2005) The role of dairy foods in weight management. Journal of the American College of Nutrition 24(6 supplement): 537S–546S.
Introduction Lipid is the collective term for a diverse range of molecules which have in common the characteristic that they are insoluble in water but soluble in organic solvents, such as ether or chloroform. This range of molecules includes triglycerides (also known as triacylglycerols), other glycerides, phospholipids, sterols, fatty acids, fat-soluble vitamins, all of which have nutritional significance. The overwhelming majority of lipid molecules in milk (approximately 98%) are triglycerides, with small amounts of sterols and phospholipids as the next most important categories. Lipids typically contribute approximately 40% of total energy in Western diets. This level has fallen slightly in recent decades in many countries due to the availability and promotion of low-fat and reduced-fat foods. Milk and milk products typically contribute about 20% of daily fat intake in Western countries, that is, approximately 8–10% of total energy intake. Lipids are significant in the diet in a wide variety of ways. They contribute to the palatability of foods by influencing taste, texture, and mouthfeel. They provide a concentrated source of food energy (9 kcal g1 or 38 kJ g1). Lipids, when deposited as body fat, help protect vital body organs and provide a store of energy for long-term exertion. Food lipids are a source of fat-soluble vitamins (A, D, E, K) and essential fatty acids (linoleic acid and -linolenic acid). Considerable research effort over many decades has focused on the health effects of food (including milk) lipids. Dietary lipid intakes have been related to the so-called ‘diseases of affluence’, such as coronary heart disease (CHD), stroke, and certain cancers. However, in discussing the putative role of dietary lipids, it is important to note the multifactorial etiology of these diseases, that is, there are other risk factors, such as cigarette smoking, hypertension, genetic factors, obesity, diabetes, and exercise level. Indeed, many other dietary factors apart from lipid intake are known to influence chronic disease risk, for example, the protective effects of high intakes of fruit and vegetables are well recognized. Thus, when discussing the health effects of milk lipids in isolation, it is important to emphasize that no food or food constituent, such as fat, should be considered healthy or unhealthy per se. All foods and food constituents are to be considered in the context of overall dietary intake, that is,
one can discuss healthy/unhealthy diets but not individual foods or food constituents.
Metabolism of Lipids Digestion Lipids are a heterogeneous group of molecules which are soluble in nonpolar solvents. Digestion of lipids must take place in the intestinal tract which is an aqueous polar environment and subsequent lipid transport in the blood is also in an aqueous environment. However, as described below, the body has devised means for overcoming this problem. Digestion of fat is initiated by the action of lingual lipase which is secreted in the mouth. However, the major site of fat digestion is the duodenum. The churning action of the stomach creates a crude oil-in-water emulsion of the fat prior to its entry into the duodenum. In the duodenum, the emulsification of fat is enhanced by the action of bile salts and phospholipids which are released from the gall bladder. Pancreatic juice supplies lipase which catalyzes the hydrolysis of triglycerides to fatty acids. Fatty acids are cleaved from positions 1 and 3 of the triglycerides, resulting in 2-monoglycerides. Pancreatic lipase has a poor ability to cleave the fatty acid from position 2. However, a process known as acyl migration may occur and the fatty acid may move to position 1 and subsequently be cleaved by lipase. Additionally, the 2-monoglycerides can be absorbed directly without further hydrolysis. Bile acids play a key role in facilitating the action of pancreatic lipase on triglycerides. The bile acid molecules have both hydrophobic and hydrophilic regions. The former region interacts with the oil surface of the fat droplets while the latter region interacts with the aqueous phase in the duodenum. The association of the bile acids with the oil droplets also results in a negative charge on the surface of the droplets. This negative charge causes pancreatic co-lipase to be attracted to the surface of the oil droplets. Thus, a complex of bile acids, pancreatic lipase, and co-lipase act at the oil–water interface to release fatty acids from the triglyceride molecules. A pancreatic cholesteryl hydrolase releases free fatty acids from any cholesteryl esters present in the duodenum. Phospholipase A cleaves fatty acids from phospholipids to form lysophospholipids.
711
712 Milk Lipids | Nutritional Significance
It has been shown that short-chain fatty acids, for example, butyric acid which is commonly found in position 3 of milk fat triglycerides, are released more rapidly from triglycerides by lipase action than longer-chain fatty acids. However, due to the relatively long time that fat resides in the duodenum, breakdown of triglycerides to fatty acids is virtually complete. However, malabsorption of fat and the appearance of significant amounts of fat in the feces (steatorrhea) may occur in diseased states if insufficient pancreatic lipase, colipase, and bile salts are secreted into the duodenum or if the intestinal mucosal cells become diseased due to severe bacterial infection or conditions such as coeliac disease.
Absorption and Transport of Fats in the Body Fatty acids with fewer than 12 carbons are generally absorbed directly across the intestinal wall into the bloodstream where they are bound to plasma albumin and transported to the liver. Long-chain fatty acids, monoglycerides, cholesterol, and lysophospholipids form micelles in the gut with bile acids. These are then absorbed by the enterocytes that line the gut. In the enterocytes, the lipid digestion products are reassembled into triglycerides, cholesterol esters, and phospholipids. These molecules are immiscible or poorly miscible with water. This is a major issue as these molecules must be transported by the blood (an aqueous environment) throughout the body. This problem is overcome by the association of absorbed lipid molecules with proteins to form lipoproteins. The proteins perform a dual role. Because of their amphiphilic nature, the proteins facilitate transport of lipids in the bloodstream. Second, the proteins (mainly a protein called apolipoprotein B-48, which is present in chylomicrons) allow the lipoprotein particles to be recognized by receptors on cell surfaces throughout the body, thus facilitating the controlled uptake of lipoprotein particles from the bloodstream. Chylomicrons are the lipoprotein particles that are assembled in the enterocytes following digestion and absorption of dietary fat from the gut. The chylomicrons enter the lymphatic system and subsequently the blood following their release from the enterocytes. The blood enzyme, lipoprotein lipase, is involved in releasing free fatty acids from triglycerides in the chylomicrons. These fatty acids are taken up by tissues (e.g., for storage as triglycerides in adipose tissue or metabolism in muscle tissue) and the remainder of the chylomicron particles (remnants) may pass to the liver. Triglycerides and cholesterol may also be synthesized directly in the liver rather than derived from the diet. The triglycerides synthesized in this manner are transported
mainly in the bloodstream in lipoprotein particles called very low density lipoproteins (VLDL). Cholesterol is transported primarily in either low-density lipoproteins (LDL) or high-density lipoproteins (HDL). Thus, all lipoproteins contain proteins, triglycerides, phospholipids, cholesteryl esters, and cholesterol in varying amounts which account for the differences in their density.
Lipids and Obesity A considerable body of evidence worldwide indicates that obesity is associated with increased risk of morbidity and mortality from chronic diseases such as CHD and certain cancers. Dietary guidelines worldwide advise individuals to maintain desirable body weight by controlling food intake and by undergoing regular aerobic exercise. It is also recognized that fat distribution in the body is important in predicting risk for chronic diseases. Central obesity, involving fat deposition around the waist and upper body, is a significant risk factor for CHD. Lower body obesity, involving fat deposition around the hips and thighs, is a much lower risk factor. As noted earlier, the energy value (known as the Atwater factor) for triglycerides is about 9 kcal g1 (38 kJ g1). This compares with approximately 4 kcal g1 (17 kJ g1) for both carbohydrates and proteins. Thus, the more fat in the diet, the more energy-dense it is. This energy density, however, makes fat a more attractive energy store in the body. The degree of digestibility of a fat influences the metabolizable energy available to the body. Most fats, including milk fat, are digested almost completely by healthy individuals. However, long-chain (over 18 carbons) saturated fatty acids are slightly less well digested and absorbed than shorter-chain fatty acids. On the other hand, medium- and short-chain fatty acids have lower metabolizable energy values as they undergo different pathways of metabolism from longer-chain fatty acids. These short- and medium-chain fatty acids are absorbed primarily into the portal blood and metabolized in the liver rather than stored in adipose tissue. Milk fat from ruminant animals contains significant amounts of short-chain fatty acids; about one-third of milk fat triglycerides contain a butyric acid residue. A number of studies have addressed the issue of whether dairy consumption is inversely associated with reduced risk of the metabolic syndrome (obesity, high blood pressure, abnormal blood lipids). Pereira and colleagues reported a 70% decrease in risk of the metabolic syndrome over a 10-year period in individuals with higher levels of dairy product intakes.
Milk Lipids | Nutritional Significance
Lipids and Coronary Heart Disease CHD is the major cause of mortality in Western societies. CHD involves the inability of the coronary arteries to supply sufficient blood, and hence oxygen, to the heart muscle, a portion of which may then die. A heart attack (infarction) is a sudden event involving blockage (thrombosis) of a coronary artery by a blood clot. If significant atherosclerosis is present, that is, an accumulation of plaque deposit in the artery lining resulting in a narrowing of the arteries, the formation of a blood clot is likely to be more serious and often fatal. The ‘lipid hypothesis’, that is, that the etiology of CHD is influenced by dietary fat intake, has been researched extensively for many decades. This hypothesis is that dietary fat, in particular saturated fat, results in an elevation of the blood cholesterol level, which over time results in atherosclerosis. Eventually, a coronary artery thrombosis may occur, resulting in a heart attack. It is thought that atherosclerosis is initiated by damage to a blood vessel wall. This damage may result from factors such as the action of lipid free radicals, reactive oxygen species, infective agents, mechanical stress due to hypertension, and autoimmune reactions. Smooth muscle cells and immune system cells known as macrophages have been shown to accumulate at the site of blood vessel damage. Lipids, principally cholesteryl esters, begin to accumulate at the point of damage as a form of plaque. This atherosclerotic plaque tends to accumulate macrophages which become engorged with lipids, principally from low density lipoprotein (LDL). These lipidengorged macrophages are known as ‘foam cells’. The ability of dietary fat intake to modulate blood lipid levels has been recognized for nearly a century. Landmark studies were conducted in the 1960s by two independent research groups led by Ancel Keys and Mark Hegsted which systematically evaluated the effects of different types of dietary lipids on blood lipid levels in human subjects maintained under strictly controlled metabolic ward conditions. The human subjects were fed a wide range of fats and oils of varying fatty acid composition. These studies led to the development of equations that predicted the changes that would occur in blood cholesterol level following changes in the intake of dietary saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), and cholesterol. Keys and Hegsted independently showed that SFAs were approximately twice as effective in raising blood cholesterol level as PUFAs. Dietary cholesterol intake had a relatively minor influence on blood cholesterol level. These early investigators studied the effects of dietary fat on total blood cholesterol and did not discriminate between different lipoprotein fractions. It is now recognized that dietary parameters influence the
713
levels of different lipoprotein fractions in different ways. Furthermore, it has been demonstrated clearly that the levels of different lipoprotein fractions are related to the risk of CHD in different ways. Elevated levels of LDL have been shown to be a major risk factor for CHD. Likewise, low levels of HDL are a risk factor for CHD. Research findings indicate that dietary intake of different SFAs influences blood cholesterol level to different degrees. Short- and medium-chain fatty acids (4:0 to 10:0), which are found in ruminant milk fat, have little or no effect on blood cholesterol level; furthermore, stearic acid (18:0) has little effect on blood cholesterol. Thus, only lauric (12:0), myristic (14:0), and palmitic (16:0) acids have a significant effect on blood cholesterol and, in particular, LDL cholesterol level. Monounsaturated fatty acids (MUFAs), in particular oleic acid (18:1), have been evaluated for their ability to influence blood cholesterol level. Data indicate that MUFAs, when substituted for SFAs, tend to reduce total blood cholesterol level and, in particular, again, LDL cholesterol. PUFAs of the n–6 family (linoleic, 18:2, being the most important in the diet) have been shown to reduce blood cholesterol level. On the other hand, PUFAs of the n–3 family (primarily -linolenic, 18:3, from plant oils and eicosapentaenoic, 20:5, and docosahexaenoic, 22:6, from fish oils) tend to lower blood triglyceride level to a greater extent than the cholesterol level. Many of the studies on the effects of fatty acids on blood cholesterol have been highly controlled experiments. Prudence is required in extrapolating the results of these studies to free-living populations where people eat a wide variety of fats as part of a mixed diet. Milk fat is hypercholesterolemic when evaluated in controlled experiments. However, epidemiological studies on freeliving populations tend to indicate that intake of milk and milk products does not increase blood cholesterol level significantly. Indeed, studies of the Masai tribe in east Africa indicate that they have very low blood cholesterol levels on a traditional diet rich in milk (primarily fermented) and other animal products. It has been suggested that the Masai may have low blood cholesterol levels due to their low caloric intake and, perhaps, an inherited ability to regulate blood cholesterol level at a low value. Other researchers have suggested that milk contains an unknown cholesterol-lowering factor which counteracts the theoretical hypercholesterolemic effect of milk SFA. However, evidence for such a factor is scant. Further work has investigated the possibility that cultured and culture-containing milk products may be hypocholesterolemic. There is some evidence that increased gut colonization by lactobacilli, whether by ingestion of culture-containing products or by
714 Milk Lipids | Nutritional Significance
manipulation of gut pH to favor lactobacilli, may modify cholesterol metabolism. However, the evidence, at best, suggests that lactobacilli are responsible for only small reductions in blood cholesterol.
Conjugated Linolenic Acid (CLA) in Milk Fat Extensive hydrogenation of ingested PUFAs occurs in the rumen of ruminants, catalyzed by the diverse microflora present. A further effect observed in the rumen is the possible disruption of the original methylene-interrupted (unconjugated) sequence of cis double bonds. Cis–trans isomerization may occur and double bonds may migrate along the fatty acid chain. A cis–trans conjugated double bond sequence may evolve: CH3 ðCH2 Þ4 CH ¼ CH CH2 CH ¼ CH ðCH2 Þ7 cis
cis
COOHð9-cis;12-cis-18:2; linolenic acidÞ
is converted to CH3 ðCH2 Þ5 CH ¼ CH CH ¼ CH ðCH2 Þ7 COOH trans
cis
ð9-cis;11-trans 18:2; conjugated linolenic acid; CLAÞ
9-cis,11-trans-CLA is the principal isomer found (about 90% of total CLA) in biological systems but other isomers of CLA have also been identified. Milk fat and dairy products have very high concentrations of CLA, which vary with season and stage of lactation. Cheese is the best dietary source of CLA, with reported levels of 0.6 mg g1 fat in blue cheese, 1.9 mg g1 fat in Parmesan, and up to 8.8 mg g1 fat in processed cheeses containing whey protein concentrate. CLA is also found in meat from ruminant animals. Over the last two decades, there has been significant research effort on the potential health effects of CLA ingestion. Data indicate that CLA is anticarcinogenic in animal models. It has been suggested that it may be partly responsible for the reduced risk of breast cancer that has been reported in women with high milk consumption. The mechanism by which CLA may exert an anticarcinogenic effect is unclear. It may act as an antioxidant, it may influence eicosanoid metabolism, and it may inhibit biosynthesis of proteins and/or polynucleotides that may be involved in the cancer process. It has been clearly shown that dietary CLA is incorporated into body tissues, such as adipose tissue, human milk, and blood cells. For example, one study has shown that the consumption of 112 g Cheddar cheese per day for 4 weeks significantly increased the level of CLA in blood.
Lipids in Infant Nutrition There is universal agreement that human milk is the most appropriate food for healthy human babies born at full term. However, as many mothers do not wish or are unable to breast feed, a need has arisen for infant formulae, most of which are based on cow’s milk. The formulae try to mimic the composition of human milk to the greatest degree possible, although it is impossible to fully achieve this objective. The concentrations of proteins and salts (sodium) in cow’s milk are too high for infants. The fatty acid composition of cow’s milk fat also differs very significantly from human milk fat. Furthermore, human milk fat tends to contain slightly more cholesterol than cow’s milk fat. The level of short-chain fatty acids (4:0, 6:0, 8:0, and 10:0) is much higher and the level of long-chain saturated acids (14:0, 16:0, and 18:0) is significantly higher in cow’s milk than in human milk fat. Conversely, the content of MUFAs (primarily 18:1 but also 16:1) is significantly higher in human milk fat. Furthermore, the level of PUFAs in human milk fat is considerably higher than in ruminant milk fat; the long-chain n–3 PUFAs, which are present at trace levels in cow’s milk fat, are present at quite high levels in human milk fat. Newborn human babies have a significant need for lipids for membrane synthesis, particularly in the brain and nervous system. High levels of arachidonic (20:4, n–6) and docosahexaenoic (22:6, n–3) are present in membrane lipids of the brain and nervous system. The levels of their respective precursors, linoleic (18:2, n–6) and -linolenic (18:3, n–3), are much lower. The optimum ratios of n–3 to n–6 fatty acids and of precursors (18:2 and 18:3) to products (20:4 and 22:6) in infant formulae have not yet been definitively elucidated. However, it has been suggested that long-chain n–3 fatty acids and long-chain n–6 fatty acids should provide 0.25–0.5% and 0.35–0.7% of energy, respectively. Furthermore, the need for n–6 linoleic and n–3 -linolenic acids has been estimated to be 5–6 and 1% of energy, respectively. In the past, higher levels of linoleic acid have been used but there is now increasing recognition of the importance of n–3 fatty acids.
Conclusions Milk lipids play a positive role in the diet as a source of energy, fat-soluble vitamins, and essential fatty acids. Milk lipids also contribute to the palatability of the diet. Concerns have been expressed regarding the hypercholesterolemic effect of dietary SFAs. Milk lipids from ruminant animals are rich in short-chain fatty acids which do not exert a hypercholesterolemic effect. Of the
Milk Lipids | Nutritional Significance
longer-chain fatty acids in milk fat, only 12:0, 14:0, and 16:0 exert a significant hypercholesterolemic effect in controlled feeding trials with human subjects. However, the evidence that milk intake in free-living populations is hypercholesterolemic is poor. There is some evidence that CLA present in milk fat may exert beneficial health effects. While a reduction in lipid intake, including milk lipids, may be beneficial for obese and overweight individuals, it is important to place a reduction of dietary fat intake for the general population in the context of the need to alter other practices such as smoking and exercise, and control of blood pressure. An optimum diet should emphasize moderation and variety. Milk and milk lipids can certainly play their part in such a diet. See also: Butter and Other Milk Fat Products: Fat Replacers. Dehydrated Dairy Products: Infant Formulae. Milk Lipids: Conjugated Linoleic Acid. Cholesterol: Factors Determining Levels in Blood; Removal of Cholesterol from Dairy Products. Nutrition and Health: Nutritional and Health-Promoting Properties of Dairy Products: Contribution of Dairy Foods to Nutrient Intake. Vitamins: Vitamin A; Vitamin E; Vitamin K; Vitamin B12; Folates; Biotin (Vitamin B7); Niacin; Pantothenic Acid; Vitamin B6; Thiamine.
Further Reading Astrup A (2006) How to maintain a healthy body weight. International Journal of Vitamin and Nutrition Research 76: 208–215. Biong AS, Miller H, Seljeflot I, Veierod MB, and Pedersen JI (2004) A comparison of the effects of cheese and butter on serum lipids,
715
haemostatic variables and homocysteine. British Journal of Nutrition 92: 791–797. Elwood PC, Pickering JE, Fehily AM, Hughes J, and Ness AR (2004) Milk drinking, ischaemic heart disease and ischaemic stroke. II. Evidence from cohort studies. European Journal of Clinical Nutrition 58: 718–724. German JB, Gibson RA, Krauss RM, et al. (2009) A reappraisal of the impact of dairy foods and milk fat on cardiovascular disease risk. European Journal of Nutrition 48: 191–203. Gurr MI (1999) Lipids in Nutrition and Health: A Reappraisal pp. 221. Bridgewater, UK: The Oily Press. Hegsted DM, McGandy RB, Myers ML, and Stare FJ (1965) Quantitative effects of dietary fat on serum cholesterol in man. American Journal of Clinical Nutrition 17: 281–295. Keys A, Anderson JT, and Grande F (1965) Serum cholesterol response to changes in the diet. IV. Particular saturated fatty acids in the diet. Metabolism 14: 776–787. Motard-Belanger A, Charest A, Grenier G, Paquin P, Chouinard Y, and Lemeieux S (2008) Study of the effect of trans fatty acids from ruminants on blood lipids and other risk factors for cardiovascular disease. American Journal of Clinical Nutrition 87: 593–599. Ness AR, Davey Smith G, and Hart C (2001) Milk, coronary heart disease and mortality. Journal of Epidemiology and Community Health 55: 379–382. Oh K, Hu FB, Manson JE, Stampfer MJ, and Willett WC (2005) Dietary fat intake and risk of coronary heart disease in women: 20 years of follow-up of the nurses’ health study. American Journal of Epidemiology 161: 672–679. Parodi PW (2009) Has the association between saturated fatty acids, serum cholesterol and coronary heart disease been over emphasized? International Dairy Journal 19: 345–361. Pereira MA, Jacobs DR, Jr., Van Horn L, Slattery ML, Kartashov AI, and Ludwig DS (2002) Dairy consumption, obesity, and the insulin resistance syndrome in young adults. Journal of the American Medical Association 287: 2081–2089. Tholstrup T (2006) Dairy products and cardiovascular disease. Current Opinion in Lipidology 17: 1–10. Tricon S, Burdge GC, Jones EL, et al. (2006) Effects of dairy products naturally enriched with cis-9, trans-11 conjugated linoleic acid on the blood lipid profile in healthy middle-aged men. American Journal of Clinical Nutrition 83: 744–753. Zemel MB (2005) The role of dairy foods in weight management. Journal of the American College of Nutrition 24(6 supplement): 537S–546S.